A Phase Ib Study Evaluating the Safety, Efficacy, Pharmacokinetics, and Pharmacodynamics of Glofitamab in Combination With Gemcitabine Plus Oxaliplatin in U.S. Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 56
- 主要终点
- Incidence of Adverse Events (AEs)
研究概览
简要总结
The purpose of the study is to evaluate glofitamab + gemcitabine + oxaliplatin in participants in the United States, including under-represented racial and ethnic populations, that have relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL).
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Histologically confirmed DLBCL, not otherwise specified (NOS)
- •Relapsed (disease that has recurred following a response that lasted ≥ 6 months after completion of the last line of therapy) or refractory ( disease that did not respond to or that progressed < 6 months after completion of the last line of therapy) disease
- •At least one prior line of systemic therapy
- •Participants who have failed only one prior line of therapy must not be a candidate for high-dose chemotherapy followed by autologous stem cell transplant (ASCT)
- •At least one bi-dimensionally measurable (> 1.5 cm) nodal lesion, or one bi-dimensionally measurable (> 1 cm) extranodal lesion, as measured on CT scan
- •Eastern Cooperative Oncology Group (ECOG) Performance Status of 0, 1, or 2
排除标准
- •Prior enrollment in Study GO41944 (STARGLO; NCT04408638)
- •Participant has failed only one prior line of therapy and is a candidate for stem cell transplantation
- •History of transformation of indolent disease to DLBCL
- •High-grade B-cell lymphoma with MYC and BCL2 and/or BCL6 rearrangements, and high-grade B-cell lymphoma NOS, as defined by 2016 WHO guidelines
- •Primary mediastinal B-cell lymphoma
- •History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies (or recombinant antibody-related fusion proteins) or known sensitivity or allergy to murine products
- •Prior treatment with glofitamab or other bispecific antibodies targeting both CD20 and CD3
- •Prior treatment with gemcitabine or oxaliplatin
- •Peripheral neuropathy or paresthesia assessed to be Grade >/= 2 according to NCI CTCAE v5.0 at enrollment
- •Treatment with radiotherapy, chemotherapy, immunotherapy, immunosuppressive therapy, or any investigational agent for the purposes of treating cancer within 2 weeks prior to first study treatment
- •Treatment with monoclonal antibodies for the purposes of treating cancer within 4 weeks prior to first study treatment
- •Primary or secondary CNS lymphoma at the time of recruitment or history of CNS lymphoma
- •Prior CNS involvement that has been definitively treated and confirmed via MRI or cerebrospinal fluid analysis to be in complete remission is permissible
- •Current or history of CNS disease, such as stroke, epilepsy, CNS vasculitis, or neurodegenerative disease
- •History of other primary malignancy, with exceptions defined by the protocol
- •Significant or extensive cardiovascular disease, or significant pulmonary disease
- •Known active bacterial, viral, fungal, mycobacterial, parasitic, or other infection (exclusing fungal infections of nail beds) at study enrollment or any major episode of infection within 4 weeks prior to the first study treatment
- •Documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection within 6 months of first study treatment, or positive SARS-CoV-2 test within 7 days prior to enrollment
- •Suspected or latent tuberculosis
- •Positive test results for hepatitis B (HBV) or hepatitis C (HCV)
- •Known or suspected chronic active Epstein-Barr viral infection
- •Known or suspected history of hemophagocytic lymphohistiocytosis (HLH)
- •Known history of progressive multifocal leukoencephalopathy
- •Prior solid organ transplantation
- •Prior allogenic stem cell transplant
- •Active autoimmune disease requiring treatment
- •Prior treatment with systemic immunosuppressive medications within 4 weeks prior to first dose of study treatment
- •Ongoing systemic corticosteroid use which, in the opinion of the investigator, puts the patient at increased risk of steroid-related iatrogenic adrenal insufficiency
- •Recent major surgery (within 4 weeks before the first study treatment) other than for diagnosis
- •Clinically significant history of cirrhotic liver disease
研究组 & 干预措施
Gemcitabine + Glofitamab + Oxaliplatin
Participants will receive a single dose of intravenous (IV) obinutuzumab pretreatment 7 days prior to the first dose of glofitamab, followed by up to 8 cycles of glofitamab + gemcitabine + oxaliplatin. This will be followed by up to 4 cycles of glofitamab monotherapy, for a total of up to 12 cycles of glofitamab (cycle length = 21 days).
干预措施: Glofitamab (Drug)
Gemcitabine + Glofitamab + Oxaliplatin
Participants will receive a single dose of intravenous (IV) obinutuzumab pretreatment 7 days prior to the first dose of glofitamab, followed by up to 8 cycles of glofitamab + gemcitabine + oxaliplatin. This will be followed by up to 4 cycles of glofitamab monotherapy, for a total of up to 12 cycles of glofitamab (cycle length = 21 days).
干预措施: Tocilizumab (Drug)
Gemcitabine + Glofitamab + Oxaliplatin
Participants will receive a single dose of intravenous (IV) obinutuzumab pretreatment 7 days prior to the first dose of glofitamab, followed by up to 8 cycles of glofitamab + gemcitabine + oxaliplatin. This will be followed by up to 4 cycles of glofitamab monotherapy, for a total of up to 12 cycles of glofitamab (cycle length = 21 days).
干预措施: Obinutuzumab (Drug)
Gemcitabine + Glofitamab + Oxaliplatin
Participants will receive a single dose of intravenous (IV) obinutuzumab pretreatment 7 days prior to the first dose of glofitamab, followed by up to 8 cycles of glofitamab + gemcitabine + oxaliplatin. This will be followed by up to 4 cycles of glofitamab monotherapy, for a total of up to 12 cycles of glofitamab (cycle length = 21 days).
干预措施: Gemcitabine (Drug)
Gemcitabine + Glofitamab + Oxaliplatin
Participants will receive a single dose of intravenous (IV) obinutuzumab pretreatment 7 days prior to the first dose of glofitamab, followed by up to 8 cycles of glofitamab + gemcitabine + oxaliplatin. This will be followed by up to 4 cycles of glofitamab monotherapy, for a total of up to 12 cycles of glofitamab (cycle length = 21 days).
干预措施: Oxaliplatin (Drug)
结局指标
主要结局
Incidence of Adverse Events (AEs)
时间窗: Up to 3 years
Complete response (CR) rate
时间窗: Up to 3 years
次要结局
- Objective response rate (ORR)(Up to 3 years)
- Duration of CR(From the first occurrence of a documented CR to disease progression or death from any cause, whichever occurs first (up to 3 years))
- Progression-free survival (PFS)(From enrollment to the first occurrence of disease progression or death from any cause, whichever occurs first (up to 3 years))
- Overall Survival (OS)(From enrollment to date of death from any cause (up to 3 years))
- Serum concentration of glofitamab(Up to 3 years)
- Duration of response (DOR)(From the first occurrence of a documented objective response to disease progression or death from any cause, whichever occurs first (up to 3 years))
- Incidence of anti-drug antibodies to glofitamab(Baseline up to 3 years)